Traditionally, pharmaceutically and therapeutically active agent agents can be administered to the body by a number of routes, including ingestion, injection, inhalation, and topical application. Absorption of an active agent by ingestion, injection, or inhalation generally gives systemic distribution of the agent throughout the body. Systemic distribution of the agent may be unsatisfactory for three reasons. First, these modes of administration produce non-specific distribution. The active agent is distributed through the entire body and not localized. Second, there may be undesirable effects such as toxic or irritating reactions on non-target organs or regions. Finally, to achieve the desired effect at the target organ or region, a higher dosage than might otherwise be desired must be administered to compensate for systemic dilution of the active agent.
In contrast to systemic delivery, topical delivery is application of an active agent in a manner so that it acts primarily at the site of application. This type of application is used typically for dermatological disorders. The above-described deficiencies of systemic delivery are not encountered when an active agent is applied topically. Rather, topical application affords the opportunity to minimize the dosage and confine the active agent to the region of the body to which it is applied. Thus, systemic distribution of the agent throughout the body is obviated. For example, ingestion of acetone could cause fetal problems which dermal delivery should avoid. Typical sites of topical delivery include application to the dermal, opththalmic, and mucous membranes and tissues, such as the hair, skin, eyes, ears, mouth, nose, throat, rectum, vagina, and urethra.
However, despite these advantages of topical delivery, most current topical delivery formulations are inefficient and therefore have limited utility. There are four reasons for this inefficiency of current topical delivery technology. First, skin and mucous membranes possess good barrier properties and the permeability of most active agents through these barriers generally is poor. Second, active agents applied topically are subject to migration and loss due to perspiration, natural tissue lavation, and mechanical action. Third, because most pharmaceutically or therapeutically active agents are relatively simple, low molecular weight compounds or mixtures, these agents are not applied alone, but in combination with a variety of additives to deliver the active agent to the application site and control the dosage. Fourth, the choice of a proper delivery system can minimize undesirable crystallization of the active agent, and hence optimize its availability in its active form. Most known topical delivery systems are petrolatum-based cremes and ointments. These unetuous formulations are unsatisfactory because they are at best uncomfortable and messy when applied.
A topical delivery system cannot be considered fully satisfactory if it is deficient with regard to any of the above-described criteria. For example, a delivery system which does not ensure that the active agent efficiently penetrates the application site is not satisfactory because it requires that an excess of agent be incorporated into the delivery system to ensure delivery of an effective quantity. The remaining active agent, i.e., that which does not penetrate the application site, is wasted. Similarly, agent which is allowed to migrate from the application site, or to crystallize before it penetrates the site, is wasted. Further, a delivery system which satisfies each criterion will be adjudged a failure by a consumer who is dissatisfied because the delivery system leaves an unpleasant residue. For example, an unctuous residue, which is unpleasant to the touch and messy, may cause a consumer not to utilize the treatment. Thus, such delivery systems are unsatisfactory.
The advantages of topical application of active agents which are bacteriostatically or fungistatically active are manifest. It also is advantageous, as described above, to apply topically treatments for lesions which result from infections such as herpes virus (types 1 and 2). Such treatments are described in U.S. Pat. No. 4,381,296 and U.S. Pat. No. 4,760,079. The former discloses a suspension of tannic acid, boric acid, and salicylic acid as the active agent, while the latter discloses that tetraethylammonium ion inhibits herpes symptoms. However, each of these treatments is unsatisfactory because each utilizes a delivery system which does not ensure that the active agents are retained at the treatment site.